POSITIVE: See Research Design and Implementation Criteria Checklist below.

Research Purpose:

To investigate the associations of plasma phospholipid concentrations of N-3 PUFAs (DHA and EPA from fatty fish and a-linolenic acid from vegetable oils) as biomarkers of intake, with the risk of incident fatal IHD and incident non-fatal MI, in older adults.

Inclusion Criteria:

Cardiovascular Health Study participants (65 years of age or older, from NC, CA, MD, PA)

Of the 54 fatal IHD cases, 36 (67%) due to arrhythmia, nine to CHF, two to other mechanisms, seven to unknown mechanisms.

Summary of Results:

Traditional IHD risk factors were generally more prevalent in cases than in controls. Cases of fatal IHD had on average higher fasting plasma glucose concentrations than did their matched controls (P=0.002) and cases of non-fatal MI were more likely than matched controls to have a higher SBP (P=0.02) and to have a family history of heart disease (P=0.047). Cases of fatal IHD were on average older than cases of nonfatal MI (P=0.0003).

After adjustment for risk factors, a higher concentration of combined DHA and EPA was associated with a lower risk of fatal IHD. For a one-SD increase in plasma phospholipid DHA and EPA, there was an associated 70% lower risk of fatal IHD (odds ratio, 0.30; 95% CI: 0.12, 0.76; P=0.01). Similarly, for a one-SD increase in a-linolenic acid, there was an associated 50% lower risk of fatal IHD (odds ratio, 0.48; 95% CI: 0.24, 0.96; P=0.04). In contrast, linoleic acid was associated with a higher risk of incident-fatal IHD. None of the PUFAs were associated with the risk of non-fatal MI.

When the analyses of fatal IHD were limited to only the cases for which the mechanism was thought to be life-threatening arrythmia (36 cases), the estimated OR of fatal IHD associated with each one-SD increase in plasma phospholipid concentrations of DHA+EPA, a-linolenic acid and linoleic acid were 0.23 (95% CI: 0.06, 0.83), 0.43 (95% CI: 0.17, 1.12) and 2.66 (95% CI: 1.04, 6.79), respectively, after adjustment for age, weight and fasting plasma glucose concentrations.

Plasma phospholipid concentrations of linoleic acid were inversely related to concentrations of combined DHA and EPA (R=-0.33, P<0.001) and positively related to concentrations of a-linolenic acid (R=0.30, P<0.0001). Similar results were obtained when the associations of combined DHA and EPA and a-linolenic acid were investigated simultaneously or separately. When the association of all three types of PUFAs were invesitgated simultaneously, the association of linoleic acid with fatal IHD was noticeably diminished.

Author Conclusion:

In this nested case-control study conducted among older adults, we found that higher plasma phospholipid concentrations of the long-chain N-3 PUFAs, DHA and EPA were associated with a lower risk of incident fatal IHD, whereas the intermediate-chain N-3 PUFA a-linolenic acid was associated with a tendency to lower risk

In contrast, higher concentrations of linoleic acid, an N-6 PUFA, were not associated with a lower risk of fatal IHD

None of these PUFAs were associated with the risk of non-fatal MI

In conclusion, our results suggest that in older adults, higher dietary intake late in life of the long-chain N-3 PUFAs, DHA and EPA found in fatty fish, is associated with a lower risk of fatal IHD

Higher dietary intake of the intermediate-chain N-3 PUFA a-linolenic acid, found in canola oil and soybean oil, also appears to be associated with a lower risk of fatal IHD

Association of the N-3 PUFAs with lower risk of fatal IHD, but not non-fatal MI, is consistent with possible antiarrhythmic properties of N-3 PUFAs.

Reviewer Comments:

Author notes that the strengths of the study include prospective study design, reliable ascertainment of cardiovascular events and the availability of information on numerous clinical characteristics collected from study participants

Study limitations include the relatively small number of incident-fatal IHD events and the indirect assessment of dietary PUFAs.

Research Design and Implementation Criteria Checklist: Primary Research

Relevance Questions

1.

Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)

Yes

2.

Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?

Yes

3.

Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to nutrition or dietetics practice?

Yes

4.

Is the intervention or procedure feasible? (NA for some epidemiological studies)

Yes

Validity Questions

1.

Was the research question clearly stated?

Yes

1.1.

Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?

Yes

1.2.

Was (were) the outcome(s) [dependent variable(s)] clearly indicated?

Yes

1.3.

Were the target population and setting specified?

Yes

2.

Was the selection of study subjects/patients free from bias?

Yes

2.1.

Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?

Yes

2.2.

Were criteria applied equally to all study groups?

Yes

2.3.

Were health, demographics, and other characteristics of subjects described?

Yes

2.4.

Were the subjects/patients a representative sample of the relevant population?

Yes

3.

Were study groups comparable?

Yes

3.1.

Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)

Yes

3.2.

Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?

If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?

N/A

3.5.

If case control or cross-sectional study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable. Criterion may not be applicable in some cross-sectional studies.)

Yes

3.6.

If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?

N/A

4.

Was method of handling withdrawals described?

Yes

4.1.

Were follow-up methods described and the same for all groups?

Yes

4.2.

Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)

N/A

4.3.

Were all enrolled subjects/patients (in the original sample) accounted for?

Yes

4.4.

Were reasons for withdrawals similar across groups?

N/A

4.5.

If diagnostic test, was decision to perform reference test not dependent on results of test under study?

N/A

5.

Was blinding used to prevent introduction of bias?

Yes

5.1.

In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?

N/A

5.2.

Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)

Yes

5.3.

In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?

N/A

5.4.

In case control study, was case definition explicit and case ascertainment not influenced by exposure status?

Yes

5.5.

In diagnostic study, were test results blinded to patient history and other test results?

N/A

6.

Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?

Yes

6.1.

In RCT or other intervention trial, were protocols described for all regimens studied?

N/A

6.2.

In observational study, were interventions, study settings, and clinicians/provider described?

Yes

6.3.

Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?

N/A

6.4.

Was the amount of exposure and, if relevant, subject/patient compliance measured?